Current drugs used in the treatment of systemic fungal infections include polyenes, azoles and nucleoside drugs which have deleterious side effects due to their cytotoxicity. Compounds which possess a narrow spectrum of target organisms are advantageous in some cases, especially when the potential for cytotoxicity in the host is reduced.
McGahren et al. have reported an unusual fungal metabolite, LL-N313.zeta., which contains a hydroxylated fused ring system similar to certain of the compounds of the present invention (J. Amer. Chem. Soc., 96:1616-77 (1974)). However, the reported compound is believed to lack the tetraene diacid half-ester possessed by the calbistrins disclosed herein, and has other structural differences at what would be C-13 of these compounds. Also, LL-N313.zeta. is reportedly inactive as an antimicrobial agent (McGahren et al., J. Org. Chem. 41:66-71 (1976)).